Our purpose is to gain a better understanding of the causes of cognitive decline and dementia through the study of brain structures at death in approximately 280 autopsied men whose health, illnesses, cognitive functioning, genetic and physiologic constitution, and midlife exposures to a long list of personal and environmental factors have been prospectively defined through repeated interview and examination over a 30+ year interval. When added to similar data already collected with prior funding (from an NIA contract) the total number of autopsies available for analysis will be approximately 640. The subjects are Japanese-American men in Hawaii aged 78+ years at death who have participated in the Honolulu Heart Program since it began in 1965. The methods for defining structural features will include gross autopsy, microscopic examination, and MRI examination of the fixed brain before dissection. Prior to fixation, multiple samples of brain tissue and CSF will be removed and frozen for future study. The specific structural endpoints to be studied include densities of neurofibrillary tangles, senile plaques, neuritic plaques, and Lewy bodies; small vessel strokes, large vessel strokes, defined changes in arterial wall architecture (medium and small vessels); brain size/atrophy (segmented into gray and white matter), and volumes of specified brain regions (hippocampus, amygdala, mesial temporal lobe, total neocortex). Analyses will be focused on: (1) autopsy verification of clinical diagnoses of dementia, (2) development of "new" neuropathologic criteria for vascular dementia, (3) identification of risk factors predicting Alzheimer's disease, vascular dementia, and the individual structural endpoints mentioned, and (4) inter-relationships among the structural endpoints as they reflect interacting processes involved ~n the pathogenesis of dementia. All methods used will allow comparisons with corresponding data generated by another study in European-ancestry women (the Nun Study). All information and materials will be archived for future research use.